tbuckley/cabot-search huggingface dataset:
Safety and feasibility of implementation of ERAS in CRS and HIPEC: Enhancing recovery or complications.
Authors: S.P. Somashekhar, Ashwin K. Rajgopal, Murthy H Srinivasa, Karnate Ramachandra, Aaron marian Fernandes, Mrudula Tatakuri, Rohit Kumar
Journal: Journal of Clinical Oncology (2023)

e18745 Background: We report our experience of implementation of ERAS protocol in patients undergoing CRS and HIPEC for peritoneal carcinomatosis. Methods: ERAS protocol for CRS± HIPEC was implemented in 90 patients from January 2021 to October 2022. We documented compliance rate and analysed the reason for non-compliance, effect of compliance on length of hospital stay, postoperative complications and readmission rate and compared the same with the 95 patients who had CRS HIPEC before adopting ERAS protocol from January 2019 to December 2020. Results: Of 185 patients in the study, 95 were in pre eras group and 90 in ERAS group. Demography, pre-operative and operative parameters were comparable between the groups. The average compliance rate achieved for entire cohort was 78.5%. Lowest compliance rates were seen for post-operative elements especially, early feeding and early mobilization. After implementation of ERAS, median length of hospital stay reduced from 12 to 9 days, length of ICU stay reduced from 4 to 2 days and postoperative complications sepsis reduced from 14.7% to 7%, respiratory complications 15.7% to 7%, surgical complications 10.5% to 2.9%, resurgery from 6.3% to 1.4% and in hospital mortality reduced from 5.3% to 1.4%. The ERAS group didn’t receive any long acting opioids, less usage of intraoperative crystalloids(7ml/kg/hr vs 13ml/kg/hr, p = 0.0001),early extubation and less readmission rates. Conclusions: The implementation of ERAS protocol is safe and feasible for CRS and HIPEC patients. Implementation of ERAS program has significantly reduced the length of hospital stay, length of ICU stay and postoperative morbidity.
Clinical trial versus standard of care in EGFR-wild type and ALK- negative lung adenocarcinoma: A propensity-matched analysis.
Authors: Hyun Ae Jung, Boram Park, Sehhoon Park, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn
Journal: Journal of Clinical Oncology (2023)

e21116 Background: Clinical trials have been a vital role for survival improvement in recurrent or metastatic lung cancer. Recent advances in targeted therapy for EGFR-mutant or ALK-positive lung adenocarcinoma dramatically increased survival. However, EGFR-wild type and ALK negative lung adenocarcinoma still had relatively poor survival outcome. Clinical trial of targeted therapy for rare driver mutation or immunotherapy was introduced in 2015. Moreover, next-generation sequencing was reimbursed in 2017 in Korea. This study evaluated the benefit of clinical trials for EGFR-wild type and ALK negative lung adenocarcinoma in recent 5 years. Methods: This study included patients with recurrent or metastatic lung adenocarcinoma who received systemic treatment between March 2017 and June 2022 at Samsung Medical Center. We compared overall survival in group with clinical trial and the standard of care (SOC) by using propensity score matching (PSM) (1:1). We used cox proportional hazard models to calculate the hazard ratio (HR) and 95% confidence interval while accounting for clustering among matched pairs. Results: Of total, 1,686 EGFR-wild type and ALK negative lung adenocarcinoma were included for final analysis. Among them, 1,380 received SOC only and 306 patients enrolled at least one clinical trial. In a group of clinical trial, 41.5%, 29.1%, and 23,2% of patients were enrolled for first-, second-, and third-line treatment, respectively. To achieve the balance between the SOC group and the clinical trial group, 8 baseline characteristics (age, sex, smoking history, ECOG performance status, brain metastasis, liver metastasis, bone metastasis, and rare driver mutation) were included. After PSM, 612 patients were matched to group of the SOC (n = 306) and the group of clinical trial (n = 306). Among the clinical trial, 27.8% was a clinical trial of targeted therapy and 72.2% was a clinical trial of immunotherapy or others. Median follow-up duration was 32.8 months (range, 5.0–64.4). Median overall survival was 17.1 months (95% CI, 13.2–21.4) for SOC and 27.3 months (95% CI, 22.1–32.4) for group of clinical trial (HR = 0.71 (95% CI, 0.58–0.88, P = 0.002). Conclusions: This study showed the performance of clinical trials for patients with EGFR-wild type and ALK-negative lung adenocarcinoma at tertiary hospital. After PSM, clinical trials showed survival benefits that reduced the risk of death by 29% in patients with EGFR-wild type and ALK-negative lung adenocarcinoma.
Treatment of extensive stage small cell lung cancer (ES-SCLC) in geriatric patients before the advent of immunotherapy: Real-life experience from one centre.
Authors: Soledad Medina, Paola Gudiel Arriaza, Angel Rodriguez, Mariana Lopez, Ana López González, Beatriz Nieto Mangudo, Manuela Pedraza, Carmen Castañon, Luis De Sande González, Juan Ignacio López Fernández, Samuel Sáez Álvarez, Pablo Segovia Alonso, Elvira Fernandez Fernandez, Manuel Fernandez Fernandez, Andrés García Palomo, Pilar Diz
Journal: Journal of Clinical Oncology (2023)

e20635 Background: SCLC is an aggressive and difficult-to-treat type of lung cancer that in recent years is increasing in incidence in those over 70 years of age. Moreover, in geriatric patients, treatment of ES-SCLC may be even more difficult due to the lack of prospective data in this more vulnerable population. In this study we will evaluate first-line chemotherapy-based treatment in the elderly. Methods: Retrospective observational trial. Patients over 70 years of age diagnosed with ES-SCLC who were treated at the Hospital Universitario de León between January 2017 and January 2022 were analysed. Data were collected from each patient's electronic medical record. To limit bias, those who had previously received treatment for limited stage or who had undergone combination chemotherapy with immunotherapy were excluded. SPSS Statics was used to analyse treatment response, 1- and 2-year survival rate, overall survival (OS) and progression-free survival (PFS). Results: 22 patients (pat.) met the elegibility criteria. Mean age 75.6 (±3.99 SD), 86.4% male (19 pat.). Eastern Cooperative Oncology Group (ECOG) score: ECOG-0 18% (4 pat.), ECOG-1 59% (13 pat.), ECOG-2 5% (1 pat.), ECOG-3 18% (4 pat.). At diagnosis, 36.4% (8 pat.) were current smokers and 63.6% (14 pat.) were former smokers; 68.2% (15 pat.) were taking more than 5 drugs. The mean Charlson scale score was 11 (±1.7 SD), while the mean Frail scale score was 2.23 (±0.97 SD). All patients received platinum-etoposide chemotherapy, 77.3% (17 pat.) with carboplatin-etoposide, 22.7% (5 pat.) with cisplatin-etoposide and of the total. There were only 6 patients with reduced starting doses and of the total patients, 54.5% (12 pat.) completed 6 cycles; 18.2% (4 pat.) 5 cycles and 27.3% (6 pat.) 2 cycles or less. Response was evaluable in 18 patients: 15 had partial response, 1 had stable disease and 2 had progression disease. At the time of analysis, there had been 21 deaths. Median OS was 10 months (95% CI 5,4-14,6) and median PFS was 6 months (95% CI 4,2-7,8). The 1-year survival rate was 45% and the 2-year survival rate was 9%. Conclusions: Despite the small number of patients, our data are similar to those obtained in the control arms of immunotherapy trials. A larger sample would be needed to consolidate our results and we plan to extend the study to other hospitals. Nevertheless, these results suggest elderly patients may benefit from treatment procedures applied in younger populations.
Genomic landscape of multiple myeloma with extramedullary disease: Results from a large patient database.
Authors: Mateo Mejia Saldarriaga, David Jayabalan, Aubrie Sowa, Jorge Monge, Cara Rosenbaum, Roger Pearse, Ruben Niesvizky, Sajay Patel, Mark Bustoros
Journal: Journal of Clinical Oncology (2023)

8058 Background: Extramedullary disease (EMD) is associated with poor outcomes and the biological mechanisms driving this phenotype are poorly understood. We used the CoMMpass registry data to explore the genomic characteristics of EMD. Methods: The CoMMpass study is a prospective, international registry of newly diagnosed MM. 1143 patients had clinical data. Patients were classified as EMD if they had EMD at any point. Genomic data from bone marrow (BM) samples at diagnosis (whole genome sequencing, whole exome sequencing (WES), and RNA sequencing (RNAseq)) were compared between EMD and non-EMD. A multivariable model was constructed based on univariable results. Differential expression (DEA) and gene set enrichment analysis (GSEA) were performed after normalization using Hallmark and MM transcriptomic subgroups. The top 24 most mutated genes in MM were selected. Results: The median overall survival (mOS) and progression free survival (PFS) was shorter for EMD. The presence of EMD, anemia at diagnosis, age &gt;65 years at diagnosis, ISS stage, and use of ASCT at the first line were independently associated with worse mOS and PFS. EMD was associated with worse mOS (HR 1.7, 95% CI 1.3 - 2.2 p &lt;0.01) and PFS (HR 1.5, 95% CI 1.23 - 1.8, p &lt;0.01) in multivariable analysis and was not abrogated by ASCT, triplet induction or maintenance. Results did not vary when landmark analysis was used. MYC amplification, deletion 18q and 1q amplification were enriched in EMD cases. TP53 mutations and TP53 bi-allelic inactivation (mutation and deletion) were enriched in EMD (Table). DEA identified 1552 genes with increased and 3344 with decreased expression (2.7%, 5.4% of total genes respectively) in EMD when compared to non-EMD. On GSEA, EMD cases were enriched for the CD-1, PR, and CTA myeloma gene expression signatures, in addition to the Hallmark pathways MYC target, E2F targets, G2M checkpoint and unfolded protein response, while the adhesion molecules pathway and MM gene signatures LB, MS, and MF were downregulated in EMD. Conclusions: EMD cases were enriched for TP53 mutations and bi-allelic TP53 inactivation, both of which are prognostic. In addition, MYC amplification, 18q deletion and 1q gain were enriched in EMD which are novel CNA associated with EMD. EMD is also enriched for distinct molecular subgroup, including enrichment for CD-1, PR, and CTA signatures, the latter two are associated with poor outcomes, and the Hallmark pathways MYC, E2F and G2M checkpoints consistent with MYC amplification and PR molecular subgroup. WES and RNAseq of matching BM and EMD tissue samples from our institution is currently being performed. [Table: see text]
Exploring the potential of combination immune checkpoint strategies in non-small cell lung cancer (NSCLC).
Authors: Aakash Desai, Vivek Subbiah, Anastasios Dimou, Jessy Deshane, Kayla Goliwas, Selvarangan Ponnazhagan, Devika Govind Das, Maya Khalil, Ying-Chun Lo, Edwin H Lin
Journal: Journal of Clinical Oncology (2023)

9037 Background: The clinical outcomes for patients with NSCLC remain suboptimal despite recent advancements in anti-PD-1/PD-L1 immunotherapies. Thus, identification of rational combinations of novel immune checkpoint (IC) strategies is imperative. This study aimed to comprehensively characterize the expression of IC targets to inform drug development and design effective combinatorial strategies, to advance the search for optimized therapies for NSCLC. Methods: We analyzed the differential gene expression of IC targets in 537 primary lung adenocarcinoma (LUAD) samples and 59 normal lung tissue samples pre-immunotherapy receipt using RNA-sequencing data from The Cancer Genome Atlas. Gene expression of IC-targets including PDCD1 (PD-1), CD274 (PD-L1), CTLA4, TIGIT, LAG3, HAVCR2 (TIM-3), VSIR (VISTA), ICOS, CD276 (B7-H3), BTLA, IDO1, KLRD1 (CD94/NKG2A), NT5E (CD73), TNFRSF4 (OX-40), TNFRSF18 (GITR), and TNFRSF9 (4-1BB) were obtained. Differential gene expression was determined intra-tumorally by comparison of transcripts per million and inter-tumorally using the DESeq2 algorithm. Log2 fold change &gt;0.5 and false discovery rate adjusted P&lt;0.05 were used as criteria for significant differential expression. Hierarchical clustering was used to identify subsets of tumors with similar profiles of IC-targetable gene expression. Results: Tumors showed significantly increased expression of TNFRSF18 (GITR), NT5E (CD73), TNFRSF9 (4-1BB), LAG3, TIGIT, CTLA4, PD-1, BTLA, B7-H3, and OX-40 (Table 1). On the other hand, tumors exhibited significant downregulation of CD274 (PD-L1), HAVCR2 (TIM-3), ICOS, KLRD1 (CD94/NKG2A), and VSIR (VISTA). Hierarchical clustering revealed recurrent patterns of IC gene overexpression which were characterized by: 1) IDO1-hi, 2) CD276-mid + TNFRSF18-mid, 3) VSIR-hi, 4) CD276-hi, 5) NT5E-hi, and 6) CD276-mid + NT5E-mid. Interestingly, patterns of IC gene expression distinguish tumors from controls. Of note, high VSIR expression was specific to normal tissue rather than tumors. Conclusions: Our study identified many IC targetable genes that were significantly overexpressed in tumors. However, subsets of tumors showed distinct and segregable combinations of overexpressed IC genes. These results suggest heterogeneous mechanisms of immune evasion in NSCLC, which may explain suboptimal outcomes with anti-PD-1/PD-L1 based strategies in this patient population. Our findings emphasize the importance of biomarker-guided approaches for the optimal selection of ICs and the development of rational combinatorial immunotherapies in NSCLC.
FGR methylation in blood as a potential marker for the pre-clinical detection of early lung cancer: A case-control study.
Authors: Rongxi Yang, Wenjing Zhang, Qiang Zhu, Yakang Song, Huapeng Song, Xiajie Zhou
Journal: Journal of Clinical Oncology (2023)

e20500 Background: Lung cancer (LC) is the leading cause of cancer-related death. Although low-dose computed tomography (LDCT) is a routine clinical test for early detection of LC, it can introduce excessive false positives. DNA specific methylation identification in peripheral blood can be used for noninvasive diagnosis and monitoring. Therefore, We applied a candidate approach and assess the association between blood-based FGR methylation and the risk of lung cancer in a case–control cohort. Methods: A total of 426 patients with LC and 428 age-and sex-matched healthy controls were recruited from two hospitals to collect peripheral blood and clinical information. The methylation levels of four CPG sites in FGR gene were determined by quantitative mass spectrometry. Linear regression models were used to estimate the association between DNA methylation site levels and lung cancer. And stratified analysis of age and sex. Results: It was found that the hypermethylation of FGR_CPG1 and FGR_CPG2 was associated with early LC (OR = 1.60 (95%CI: 1.35, 1.89, p = 5.35E-08) and 1.08 (95%CI: 1.01, 1.16, p = 3.58E-02), respectively). These associations persist in patients with very early LC (stage I). Stratified analysis showed that the association between hypermethylation of FGR_CPG2 and LC was only found in men and subjects younger than 55 years of age. Conclusions: This work reveals a novel association between aberrant FGR gene methylation in blood and early LC. These results suggest that FGR gene methylation may be used to predict early lung cancer and provide guidance for the prevention and control of lung cancer.
Distant stage melanoma incidence among US adult women.
Authors: Caitlin Ruth Johnson, Cheng-I Liao, Bianca Obiakor, Ruolin Lorraine Jiang, Daniel Stuart Kapp, John K Chan
Journal: Journal of Clinical Oncology (2023)

e21555 Background: To examine trends in distant stage melanoma incidence among U.S. women. Methods: Demographic and clinical data were obtained from the United States Cancer Statistics (USCS) Database from 2001-2019. SEER*Stat 8.3.9.2 and Joinpoint regression program 4.9.0.0 were used to calculate cancer incidences and trends per 100,000. Average annual percentage change (AAPC) was used to describe trends. Age-adjusted incidences were adjusted by the U.S. 2000 standard population. Results: From 2001-2019, 543,051 women were diagnosed with distant stage melanoma. Over this period, incidence rose from 0.37 to 0.59/100,000 with an increasing annual rate of 2.58% per year (p &lt; 0.0001). In 2019, non-Hispanic White women had disproportionately higher incidence rates at 0.76/100,000 compared to Hispanic (0.26/100,000), non-Hispanic Black (0.17/100,000), and non-Hispanic Asian (0.08/100,000) women. Regarding race, the largest increase in distant melanoma incidence was observed in White women with an average annual increase of 2.92% (p &lt; 0.0001). Among age groups, incidence was highest among those aged ≥45 (1.54/100,000) and 40-44 (0.53/100,000) years. However, the largest increases in distant melanoma incidence were found among 30-34-year-olds at a rate of 3.91% per year (p = 0.004) and 40-44-year-olds at 2.78% per year (p = 0.003). When examined by race and age, annual incidence rates were highest among White women aged 40-44 years at 3.68% per year (p &lt; 0.0001). Regarding U.S. state, incidence was highest in Florida (1.34/100,000), West Virginia (1.32/100,000), and Oklahoma (1.20/100,000). The largest annual increases in distant melanoma incidence rates were observed in Nebraska at 8.63% (p = 0.001), Kentucky at 6.18% (p &lt; 0.0001), and West Virginia at 6.06% (p = 0.001). When performing an intersection analysis of race, age, and U.S. stage, White women living in Nebraska aged ≥45 had the largest increase in distant melanoma at a rate of 8.12% annually (p = 0.004). In 2019, White women in Utah had the highest incidence of distant melanoma at 3.45/100,000. Conclusions: Distant stage melanoma is disproportionally increasing among adult women aged 30-44 years, especially among White populations. Further studies are warranted to understand the environmental and socioeconomic implications behind these trends.
Immunogenicity after COVID-19 vaccination in patients with solid tumor and hospital staff: A prospective single-center observational study.
Authors: Yuki Katsuya, Tatsuya Yoshida, Shu Yazaki, Shigehiro Yagishita, Hiroko Nakahama, Osamu Kobayashi, Masatoshi Yanagida, Yasuhiro Irino, Akinobu Hamada, Noboru Yamamoto
Journal: Journal of Clinical Oncology (2023)

10626 Background: Patients with tumor are at high risk of severe COVID-19, and vaccination against SARS-CoV-2 is recommended. Impact of cancer treatment on immunogenicity has not been evaluated well. Methods: This prospective study was conducted to assess the seroconversion rate of SARS-CoV-2 vaccines among patients with cancer and hospital staff. Further, we focused on the difference among cancer treatment regimens. SARS-CoV-2 spike protein-specific IgG (S-IgG) were evaluated before the first vaccination, 1–3 months, 4–6 months, and 7–12 months after the second vaccination, and 1–3 months after the third vaccination. The primary endpoint was seroconversion rate measured 1–3 months after the second vaccination. Results: From April 2021 to November 2021, consent was obtained from 629 cancer patients and 210 hospital staff. Excluding missing data and withdrawal of consent, 590 cancer patients and 183 hospital staff without complications was analyzed. At 1–3 months after the second vaccination, S-IgG antibody concentration higher than the cut-off value (20 BAU/mL) was found in 96.1% (567/590) patients with cancer and 100% (183/183) of the healthy controls (p = 0.0024). At 4–6 months after second vaccination, S-IgG antibody concentration higher than the cut-off value was found in 93.1% (461/495) patients with cancer and 100% (170/170) of the healthy controls (p &lt; 0.0001). The significant difference in seroconversion rate between the two groups persisted even after 7-12 months. Patients undergoing treatment regimens such as platinum combination therapy (median: 423.7, 95% CI: 264.2–767.0, p = 0.003) and alkylating agent (median: 57.5, 95% CI: 5.4–748, p &lt; 0.0001) among cytotoxic drugs, and PARP inhibitor (median: 264, 95% CI: 43–690.4, p = 0.0004), mTOR inhibitor (median: 227.4, 95% CI: 5.7–323.4, p = 0.0036), BCR-ABL inhibitor among drugs (median: 124.4, 95% CI: 0.0–288.9, p = 0.005) among target molecule drugs showed lower antibody titer compared to the no-treatment patients with cancer group. Conclusions: SARS-CoV-2 vaccine immunogenicity was low among patients with cancer compared to healthy control. Also, several treatment regimens were found to negatively impact immune response. Clinical trial information: UMIN000049403 , UMIN000049430 . [Table: see text]
Prognostic value of month 1 bone marrow and PET MRD status in CAR-T therapy for myeloma.
Authors: Radhika Bansal, Jeffrey Babcock, Larissa Brunaldi, Saurabh Chhabra, Ricardo Daniel Parrondo, Morie A. Gertz, Matthew Hathcock, David Dingli, Prashant Kapoor, Taxiarchis Kourelis, Joselle Cook, Suzanne R. Hayman, Rahma M. Warsame, Moritz Binder, Rafael Fonseca, Peter Leif Bergsagel, Sikander Ailawadhi, Shaji Kumar, Stephen M Broski, Yi Lin
Journal: Journal of Clinical Oncology (2023)

8024 Background: Minimal residual disease (MRD) is prognostic for survival in multiple myeloma (MM). MRD is usually assessed in the bone marrow (BM) by flow cytometry or NGS. MRD by FDG PET/CT provides a global representation of the tumor burden, including response assessment of extramedullary disease. We examined MRD status in MM pts using both BM and PET/CT at Mayo Clinic. Methods: Medical records were reviewed retrospectively for MM pts who received CAR-T between 4/2018 and 12/2022. All PET/CT scans were assessed by radiologists. BM MRD was assessed by flow cytometry with a sensitivity of 10 -5 . Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method. Results: Among the 157 CAR-T pts, including 89 pts who received FDA-approved CAR-T, median age was 63 years, 59% (92/157) were males, 42% (66/157) had high risk cytogenetics with median of 5 prior lines of therapy, 36% (57/157) had plasmacytoma. Incidence of CRS was 83%, 5% grade ≥ 3 CRS. Incidence of ICANS was 19%, 4% grade ≥ 3 ICANS. CR/sCR rate was 37%. One hundred and thirty-seven pts (87%) had evaluable BM at month (mo) 1, 85% (117/137) were BM MRDneg at mo 1. Baseline demographics were comparable between the two groups except age, % BM plasma cells and use of bridging therapy. Among the MRDneg pts, CR/sCR rate was 44% (51/117) and 95% (111/117) had sFLC below normal. At median follow-up of 13.8 months, median PFS among pts with BM MRDneg at 1 mo was 12 mo (95% CI: 11, 30) vs 3 mo (95%CI: 2, 7) for BM MRDpos (p&lt;0.001). Median OS among pts with BM MRDneg at 1 mo was 34 mo (95% CI: 24, NR) vs 22 mo (95%CI: 7, NA) for BM MRDpos (p&lt;0.01). At month 1, 112 pts had both BM and PET/CT assessments available, 64/112(57%) were both BM MRDneg/PET MRDneg, 38/112 (34%) were MRDneg for either BM or PET and 10/112 (9%) were positive for both BM and PET (MRDpos/PET MRDpos). Baseline demographics except age were comparable between the 2 groups (Table). Rate of conversion from MRDpos to MRDneg was low. Rate of sustained BM and PET MRDneg at mo 12 was 44% (8/18). The median PFS and OS for BM MRDneg/PET MRDneg was significantly longer as compared to others (Table). Conclusions: Achieving FLC below normal, BM MRDneg and PET MRDneg at 1 month, regardless of IMWG response at that time, is prognostic for both PFS and OS in MM pts receiving CAR-T. Failure to achieve any of these confers poor prognosis. [Table: see text]